Imaging complex organ-on-chip systems

Oral drug delivery is a preferred method for drug administration because it is economical and convenient to the patient [1]. Uptake from the gut to the blood is mediated by the intestinal barrier, which exhibits some selectivity, i.e., mechanisms in the intestinal barrier define which compounds are absorbed and which are not. The limited understanding of these mechanisms impedes the design and development of new oral drugs. On the horizon: Emerging organ-on-a-chip models of the intestine may provide new insights into structure-function relationships in biological barriers like the gut-blood interface of the intestine. These small ‘artificial organs’ can host biological cells, which mimic the natural behavior of intestinal cells, thus providing a highly controlled platform for fundamental bioresearch and, ultimately, drug-screening [2]. Our group develops and implements optical imaging technologies specifically geared for imaging organ-on-a-chip systems. At the SPIE conference “Optical Methods for Inspection, Characterization, and Imaging of Biomaterials V” we will present the application of two-photon microscopy for imaging of relatively thick 3D printed organ-on-a-chip systems and discuss imaging-challenges related to sample-induced aberrations and scattering. We will also present our ongoing work to implement an adaptive optics-enabled lattice light sheet microscope [3], which (we anticipate) will enable high-resolution imaging inside complex organ-on-a-chip systems by compensating the sample-induced aberrations. [1] P. Viswanathan, Y. Muralidaran, and G. Ragavan, "Challenges in oral drug delivery: a nano-based strategy to overcome", Nanostructures for Oral Medicine, Elsevier (2017) 173-201. [2] R. Zhang and N.B. Larsen, "Stereolithographic hydrogel printing of 3D culture chips with biofunctionalized complex 3D perfusion networks", Lab on a Chip 17.24 (2017) 4273-4282. [3] T. Liu, S. Upadhyayula, et al., "Observing the cell in its native state: Imaging subcellular dynamics in multicellular organisms", Science 360.6386 (2018) eaaq1392.